Efficacy and Safety of Ketamine/Esketamine in Bipolar Depression in a Clinical Setting.

Background: Bipolar disorder represents a significant source of morbidity and elevated mortality risk. Ketamine has emerged as a powerful antidepressant; however, there have been few trials of ketamine in bipolar depression and no trials with esketamine in bipolar depression, and few data exist from real-world settings. Here, we report outcomes from a cohort of patients with bipolar depression treated with ketamine/ esketamine in a real-world setting.Methods: Patients with treatment refractory bipolar depression were referred to Yale Psychiatric Hospital Interventional Services for treatment from October 2014 to November 2023. Appropriate patients were treated with intravenous (IV) ketamine (0.5 mg/kg over 40 minutes) or intranasal esketamine (56 or 84 mg). Diagnosis of bipolar depression was done by clinical evaluation by an attending psychiatrist, based on DSM criteria. Clinical outcomes were tabulated from medical records.Results: Overall, 45 patients with bipolar depression were treated with IV ketamine or intranasal (IN) esketamine during the time period specified. Depression severity outcomes were available for 38 patients that completed an acute series, defined as treatment twice weekly for up to 4 weeks. Overall, 15/38 (39%) achieved clinical response (≥50% improvement on the Montgomery-Asberg Depression Rating Scale [MADRS]) and 5/38 (13.2%) achieved remission (≤10 on MADRS) following the acute series. Mean MADRS scores decreased from 31.1 to 19.2 (38.3% mean improvement). Safety data (hypomania/manic symptoms) were available for all 45 patients (518 patient-months of follow-up). No patients experienced any mania/hypomania during the acute series phase (when treatments are given twice weekly). However, 13/45 (28.9%) patients experienced symptoms consistent with a hypomanic or manic episode at some point following the acute phase while continuing to receive ketamine or esketamine during a maintenance phase. There were 16 manic/hypomanic events, indicating 1 event for every 2.7 patient-years. Only 1 event was severe and resulted in hospitalization.Conclusion: In a small sample of patients with bipolar depression treated with ketamine/esketamine, no evidence of mania/hypomania was seen during the acute phase of treatment. Further research is needed to evaluate whether ketamine or esketamine confers heightened risk of affective switch during maintenance treatment.

Efficacy, Safety, and Tolerability of Psychedelics in Treatment-Resistant Depression (TRD).

Major depressive disorder (MDD) is a highly prevalent psychiatric disorder, associated with substantial burden and large economical costs. Notwithstanding various conventional antidepressant treatment options, a large portion of depressed people (ca. 30%) fails to respond to first-line treatment, resulting in treatment-resistant depression (TRD). Although non-response to multiple antidepressant interventions is a common outcome, a consensus definition of TRD is not yet available. In practice, TRD is applied when two or more successive treatments with different antidepressants are not working. The last decade's intense research into new medicines for TRD has led to two developments, using typical or serotonergic (psilocybin, ayahuasca) and atypical (glutamatergic) psychedelics (ketamine, esketamine). Both approaches, although via different entrance mechanism, exhibit a fast onset but also long-lasting antidepressant effect far beyond the biological presence of the drug in the body, strongly indicating that downstream mechanisms activated by signaling cascades in the brain are involved. The present chapter describes the clinical development of psilocybin and esketamine for TRD and discusses the problems involved in the use of a proper placebo because of the psychotomimetic (psilocybin) or dissociative (ketamine) effects that interfere with performing "blind" studies. Nevertheless, intranasal esketamine was developed and approved for TRD, whereas psilocybin has shown positive results. Adverse effects and tolerability of both drugs in the dose ranges used are generally acceptable. The emergence of anti-TRD medicines for treatment of a very severe disease is a breakthrough in psychiatry.

[Treatment of New Daily Persistent Headache With Esketamine: Report of One Case].

New daily persistent headache (NDPH) is a kind of persistent headache that patients can identify the exact date of the sudden onset.It is one of the rare primary headaches difficult to be cured and may lead to disability,seriously affecting the daily life and work.The exact pathogenesis of NDPH remains unclear,which makes the treatment difficult.Here we report a case of refractory NDPH treated by intravenous injection of esketamine at a sub-anesthetic dose.

Efficacy and safety of esketamine hydrochloride adjunct to sufentanil in non-surgical patients under mechanical ventilation in the ICU (SENSATION trial): protocol for a multicentre, single-blind, randomised controlled trial.

INTRODUCTION: Pain is common in patients receiving mechanical ventilation in the intensive care unit (ICU). Intravenous opioids are recommended as first-line therapy for pain management; however, opioids have adverse side effects. Based on low-quality evidence, low-dose ketamine is therefore recommended as an opioid adjunct to reduce opioid consumption. Esketamine is an alternative to ketamine with greater efficacy and fewer side effects. However, evidence on the use of esketamine in patients receiving mechanical ventilation is lacking. This study investigates the efficacy and safety of esketamine as an adjunct to sufentanil for analgesic therapy in non-surgical ICU patients under mechanical ventilation. METHODS AND ANALYSIS: This ongoing multicentre, single-blind, randomised controlled trial is being conducted at six ICUs in China. 132 non-surgical patients under mechanical ventilation will be randomly assigned to the standard care and S-ketamine groups at a 1:1 ratio. Patients in the standard care group received a minimal dose of sufentanil as the sole analgesic agent. Patients in the S-ketamine group received a minimal dose of sufentanil in addition to an esketamine infusion at a fixed rate of 0.2 mg/kg/hour for analgesia. The primary outcome is mean hourly sufentanil consumption during the treatment period. ETHICS AND DISSEMINATION: This study was approved by the Ethics Committee of Chongqing University Cancer Hospital (CZLS2022067-A). Participants are required to provide informed consent. The results of this trial will be reported in peer-reviewed journals and presented at conferences. TRIAL REGISTRATION NUMBER: ChiCTR2200058933.

Effects of adjunctive esketamine on depression in elderly patients undergoing hip fracture surgery: a randomized controlled trial.

BACKGROUND: Depression is a prevalent perioperative psychiatric complication among elderly hip fracture patients. Esketamine has rapid and robust antidepressant effects. However, it is unknown whether it can alleviate depressive symptoms in elderly patients who undergo hip fracture surgery. This study aimed to explore whether the adjunctive esketamine in patient-controlled intravenous analgesia (PCIA) could improve depressive symptoms in elderly patients undergoing hip fracture surgery. METHODS: A single-center, prospective, double-blind and randomized controlled clinical trial was carried out from July 2022 to August 2023 at the Wenzhou People's Hospital among 90 patients, aged ≥ 65 years with hip fracture undergoing elective surgery. Participants were randomly allocated to either the esketamine group (group S) or the control group (group C). In Group S, patients were administered 0.5 mg/kg of esketamine as a PCIA adjuvant for 48 h, while the control group received saline. The primary outcome was the assessment of depressive symptoms using the Geriatric Depression Scale-15 (GDS-15) on postoperative day 2. The secondary outcomes were assessments of depressive symptoms on postoperative day 7 and postoperative day 30, serum levels of brain-derived neurotrophic factor (BDNF) and 5-hydroxytryptamine (5-HT), postoperative pain intensity, the number of effective PCIA presses, sufentanil consumption, and adverse events. RESULTS: The prevalence and GDS-15 scores of depression were significantly lower in group S on postoperative day 2 (28.6% vs. 53.5%; 3.5 ± 1.8 vs. 4.3 ± 1.7, P < 0.05). In group S, the number of effective PCIA presses was significantly lower on postoperative day 2 than that in group C [2(1-4) vs. 1(0-2), P<0.05]. Higher levels of BDNF (23.8 ± 1.7 ng/mL vs. 25.3 ± 2.0 ng/mL, P < 0.05) and 5-HT (219.5 ± 19.5 ng/mL vs. 217.0 ± 22.2 ng/mL, P < 0.05) in the blood were observed on postoperative day 2 in group S. CONCLUSION: In elderly patients aged ≥ 65 years undergoing hip fracture surgery, the administration of adjunctive esketamine in PCIA could improve depressive symptoms and increase levels of BDNF and 5-HT in the blood. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2200061956 (Date: 13/07/2022).

Statewide Ketamine and Esketamine Prescribing Trends in Rhode Island, 2017-2023.

Ketamine is a versatile anesthetic that has been widely used off-label to treat a variety of indications. Esketamine, a derivative of ketamine, is FDA-approved to treat treatment-resistant depression. This report compares statewide prescription ketamine and esketamine trends. Using PDMP data from 2017-2023, prescription and prescriber characteristics, and patient demographics were compared between esketamine and ketamine prescriptions. During this time, ketamine prescriptions, patients, and providers rose 55.8%, 30.6%, and 2.8% since 2017. Esketamine prescriptions increased 1289.4% since 2019. In 2023, ketamine prescriptions were primarily in powder form (98.7%) and paid for out-of-pocket (83.9%), whereas esketamine prescriptions were primarily paid for by insurance (80.2%). The proportion of ketamine prescribed in RI but dispensed out-of-state have increased 22% since 2022 (18% of total dispensations). As more people seek treatment for mental health disorders, ketamine and esketamine prescriptions continue to rise. Understanding ketamine and esketamine use can help mitigate associated adverse events.

Opioid-free anesthesia improves postoperative recovery quality of small and medium-sized surgery: a prospective, randomized controlled study.

BACKGROUND: Opioid anesthesia (OA) is currently the predominant anesthetic method. However, its associated side effects, such as nausea and vomiting, coupled with the principle of enhanced recovery after surgery (ERAS), have spurred the adoption of opioid-free anesthesia (OFA) in select surgical procedures. For small and medium-sized operations, ERAS is particularly important. The aim of this study was to investigate the effect of OFA, utilizing esketamine in combination with dexmedetomidine and sevoflurane, on postoperative recovery quality following small and medium-sized surgical interventions. METHODS: A total of 120 patients who underwent various small and medium-sized operations were randomly allocated to OFA and OA groups. The OA group received sufentanyl and sevoflurane, while the OFA group received esketamine, dexmedetomidine, and sevoflurane. The primary outcome measure was the postoperative quality of recovery-40 scores (QoR-40) 24 hours after surgery. Secondary outcomes included hemodynamic changes at different time intervals, the incidences of adverse events were recorded. RESULTS: Patients in the OFA group exhibited a higher QoR-40 score of 184.0 (182.0, 186.2) compared to 182.0 (180.0, 184.0) in the OA group (P<0.001). The disparities were particularly noble in terms of Physical comfort and Emotional status. Multivariable analysis identified postoperative nausea and vomiting (PONV) as a significant independent factor impacting QoR-40 (ß=-4.49 [-6.1, -2.87], P<0.001). Hemodynamic stability was more pronounced in the OFA than in the OA group. The incidence of PONV was substantially lower in the OFA group (one [1.6%] vs. 14 [25%], P<0.001), with a reduced need for vasoactive drugs (five [7.8%] vs. 15 [26.8%], P=0.005), and a lower incidence of respiratory depression (0 [0%] vs. six [10.7%], P=0.009). CONCLUSIONS: OFA improves the postoperative recovery quality in small and medium-sized surgical procedures, potentially attributed to decreased incidence of PONV. Additionally, OFA facilitates the maintenance of more stable hemodynamics throughout the operation.

Polish standard of treatment with racemic ketamine for patients with depressive disorders developed by a Working Group appointed by the National Consultant in the field of psychiatry. / Polski standard leczenia racemiczna ketamina pacjentów z zaburzeniami depresyjnymi opracowany przez zespól roboczy powolany przez Konsultanta Krajowegow dziedzinie psychiatrii.

The Polish standard of treatment with racemic ketamine for patients with depressive disorders was developed by a Working Group appointed by the National Consultant in the field of psychiatry. Despite the wide range of available medications, as many as one-third of depressed patients do not respond to standard antidepressant treatment, raising the need for an ongoing search for new effective and safe therapies. In recent years, the possible role of overactivity of the glutamatergic system in the etiopathogenesis of depression has again attracted the attention of many experts. The possibility of using substances with a modulating effect on the glutamatergic system in the treatment of depressive disorders has been postulated, among others, the long-known anesthetic ketamine, which is a noncompetitive NMDA receptor antagonist. This paper summarizes the results of studies on the efficacy and safety of racemic ketamine (administered intravenously) in the treatment of patients with depressive symptoms in the course of both unipolar and bipolar affective disorder, and, meeting the expectations of many practicing psychiatrists wishing to broaden the range of therapies offered to their patients, presents recommendations on indications, contraindications, precautions and the treatment regimen itself with intravenous ketamine for patients with mood disorders.

Management Strategies for Patients with Non-Infectious Cystitis: A Review of the Literature.

PURPOSE OF REVIEW: The management of noninfectious cystitis continues to evolve as new treatments continue to be developed and investigated. This review aims to synthesize the most recent data regarding management strategies for noninfectious cystitis focused on non-ulcerative, ulcerative, eosinophilic, and ketamine-induced cystitis. RECENT FINDINGS: Several novel treatments have shown promise as management options including combination antihistamine therapy, phosphodiesterase 5 inhibitors, alpha lipoic acid supplements, and onabotulinumtoxin A. Recent studies have also found pentosan polysulfate sodium to have adverse ophthalmologic effects. For patients with ulcerative cystitis, recent research has shown that fulguration with or without triamcinolone injections should not be delayed. The treatment of noninfectious cystitis should be patient specific based on factors including etiology and symptom profile. Multimodal regimens are often the most effective. Treatment should be started with conservative options and escalated as necessary to oral treatments, intravesical options, or procedural management.

A combined treatment for self-traumatic chronic skin lesions associated with post-surgical neuropathic pain in a domestic cat: a pharmacological and cold atmospheric plasma approach.

Cold atmospheric plasma (CAP) has been employed as a therapy against both acute and chronic skin lesions, contaminated or not, and has effects on angiogenesis and reepithelialization promoting healing. In this context, the present study aimed to evaluate the effects of a CAP jet associated with pharmacological treatment described by the 2015 AAHA/AAFP pain management guidelines and the 2022 WSAVA guidelines for the recognition, assessment, and treatment of pain, on the healing of chronic skin lesions caused by a pruritic reaction resulting from post-surgical neuropathic pain. To this end, a single CAP application was performed on a feline patient with a 6 months old recurrent contaminated cervical skin lesions along with administration of ketamine (10 µg/kg/min) following the prescription of prednisone (1 mg/kg, SID, 6 days), gabapentin (8 mg/kg, BID, 60 days) and amitriptyline (0.5 mg /kg, SID, 60 days). A single application of plasma associated with an NMDA antagonist, anti-inflammatory steroid, tricyclic antidepressant and gabapentinoid thus provided a significant improvement in the macroscopic appearance of the lesion within 10 days, and the owner reported the cessation of intense itching within the first four hours after treatment and a consequent improvement in the animal's quality of life. The medical treatment was finished almost a year since the writing of this paper, without clinical or reported recurrent signs of the condition. Therefore, we observed that single dose CAP application associated with ketamine, gabapentin, amitriptyline and prednisone leads to significant healing of chronically infected skin lesions resulting from post-surgical neuropathic pain.

Comparing the Sedative Effects of Intranasal Dexmedetomidine, Midazolam, and Ketamine in Outpatient Pediatric Surgeries: A Randomized Clinical Trial.

Background: The management of preoperative anxiety in pediatric patients, as well as its implications, has remained challenging for anesthesiologists. In this study, we compared the safety and efficacy of intranasal dexmedetomidine, midazolam, and ketamine as surgical premedication in children. Methods: This double-blinded randomized clinical trial was conducted at two tertiary hospitals in January 2014, on 90 children aged between 2-7 years old. The participants' American Society of Anesthesiologists (ASA) physical status was I or II, and they were scheduled for elective unilateral inguinal herniorrhaphy. Using the block randomization method, the patients were randomly assigned to three groups, each receiving intranasal dexmedetomidine (2 µg/Kg), midazolam (0.2 mg/Kg), and ketamine (8 mg/Kg) 60 min before induction of anesthesia. Anxiety and sedation state were evaluated before drug administration, and then every 10 min for the next 50 min. Parental separation anxiety, mask acceptance, postoperative agitation, pain, nausea, and vomiting were also recorded and compared between these groups. All the statistical analyses were performed using SPSS software (version 21.0). P<0.05 was considered statistically significant. Results: Ketamine indicated the strongest sedative effect 10, 20, and 30 min after administration of premedication (P<0.001, P=0.03, P=0.01, respectively). However, dexmedetomidine was more effective than other drugs after 40 and 50 min (P<0.001). Other variables indicated no statistically significant difference. Conclusion: In case of emergencies, intranasal ketamine, with the shortest time of action, could be administered. Intranasal dexmedetomidine, which was revealed to be the most potent drug in this study, could be administrated 40-50 min before elective pediatric surgeries.Trial registration number: IRCT2013081614372N1.

Intravenous patient-controlled analgesia with esketamine improves early depressive symptoms in patients with postherpetic neuralgia: a single-center retrospective cohort study.

OBJECTIVE: Patients with Postherpetic Neuralgia (PHN) often exhibit depressive-like symptoms, significantly impacting their quality of life. Esketamine, known for its analgesic properties, has also been recognized for its rapid antidepressant effects. However, its efficacy in the treatment of PHN requires further exploration. This study aims to evaluate the impact of intravenous patient-controlled analgesia(PICA) with esketamine on depressive mood in PHN patients. METHODS: This retrospective study analyzed PHN patients hospitalized and treated at the affiliated hospital of Southwest Medical University from June 2021 to March 2023. Patients were divided into the esketamine group (E group) and the sufentanil group (S group) based on their treatment regimens. Primary outcomes included pain numerical rating scale(NRS), depression patient health questionaire-9(PHQ-9), and anxiety generalized anxiety disorder-7(GAD-7) scores measured before treatment, and at 3 days, 7 days, 1 month, 2 months, and 3 months post-treatment. RESULTS: A total of 83 patients were included in the analysis. Before treatment, there were no statistically significant differences in pain NRS, depression PHQ-9, and anxiety GAD-7 scores between the two groups (P > 0.05). Compared to before treatment, significant reductions in pain NRS scores were observed at all post-treatment time points in both groups (P < 0.05), with no differences between groups (P > 0.05). The E group exhibited significantly lower depression PHQ-9 scores than the S group at 3 days and 7 days post-treatment (P < 0.05), but no significant differences were observed at 1 month, 2 months, and 3 months (P > 0.05). Anxiety GAD-7 scores were significantly lower in the E group compared to the S group at 3 days, 7 days post-treatment (P < 0.05), with no statistical differences at 1 month, 2 months, and 3 months post-treatment (P > 0.05). CONCLUSION: Both PICA with esketamine and sufentanil alleviated pain equally in PHN patients. However, PICA with esketamine specifically improved early symptoms of anxiety and depression.

[Psychedelic and dissociative agents in psychiatry: challenges in the treatment]. / Psychedelika und Dissoziativa in der Psychiatrie: Herausforderungen in der Behandlung.

With the discovery of the antidepressive effects of ketamine and the increasing withdrawal of the pharmaceutical industry from the development of new psychotropic drugs, the psychiatric research into the clinical application of hallucinogens in psychiatry has literally blossomed in the last two decades. Promising results for various treatment approaches with psychedelic agents, such lysergic acid diethylamide (LSD) and psilocybin, and dissociative agents, such as ketamine and esketamine, have raised great hopes among researchers, clinicians and patients in recent years, so that there was already talk of a new era in psychiatry. As one of the first of these substances, in December 2019 intranasal esketamine was approved in the USA and the EU for the treatment of treatment-resistant depression and Switzerland followed in 2020. Recently, psilocybin was approved in Australia, Canada and Switzerland for compassionate use in exceptional cases for the treatment of depression, while large approval studies with various psychedelic agents are currently ongoing worldwide. The medical application of psychedelic agents and ketamine/esketamine is considered to be safe; however, as with all new forms of treatment it is of crucial importance that, in addition to the hopes, the specific challenges of these new treatment approaches must also be carefully considered and assessed. Excessive expectations and an insufficient risk-benefit estimation are detrimental to the patients and the reputation of the treating physician. Although a possible paradigm shift in the care of mental health is already being discussed, this review article consciously concentrates on the possible risks of treatment and the methodological weaknesses of the studies carried out so far.

IN Esketamine and IV Ketamine: Results of a multi-site observational study assessing the effectiveness and tolerability of two novel therapies for treatment-resistant depression.

Intravenous (IV) ketamine and intranasal (IN) esketamine are novel therapies to manage treatment resistant depression within major depressive disorder (MDD-TRD). This is a multi-site observational study aiming to assess the real-world effectiveness and tolerability of these novel therapies in the management of MDD-TRD. 53 patients were referred to receive IV ketamine (n = 26, 69.23 % female, 52.81 ± 14.33 years old) or IN esketamine (n = 27, 51.85 % female, 43.93 ± 13.57 years old). Treatment effectiveness was assessed using the Montgomery and Åsberg Depression Rating Scale (MADRS) for depression severity and item 10 of the MADRS for suicidal ideation (SI). Tolerability was assessed by systematically tracking side effects and depersonalization using the 6-item Clinician administered dissociative symptom scale (CADSS-6). The data was analyzed using descriptive statistics, risk ratio and effect size. Both IV ketamine and IN esketamine significantly reduced depressive symptoms and suicidal ideation by treatment endpoint. Patients receiving IN esketamine, and patients receiving IV ketamine had a similar risk of developing side effects. All side effects reported were mild and transient. These results suggested that both IV ketamine and IN esketamine are effective in the management of depressive symptoms and were well tolerated. Therefore, the results of this study could serve to inform clinical practice.

[Comparison of the preclinical quality of analgesia of emergency physicians and paramedics based on trauma patients]. / Vergleich der präklinischen Analgesiequalität von Notarzt und Notfallsanitäter anhand traumatologischer Patienten.

BACKGROUND: Adequate prehospital pain management is a critical component of emergency medical services. With the introduction of the paramedic profession and the Paramedics Act in Germany, the basis for more extensive competencies of paramedics was established. In many emergency medical service areas it is thus possible for paramedics to perform analgesia and sedation with esketamine/midazolam according to pre-established instructions and/or standard operating procedures. This study assessed the quality of analgesia administered to trauma patients by paramedics compared to emergency medical service physicians. MATERIAL AND METHODS: The study included trauma patients who received prehospital administration of analgesia by either emergency medical service physicians or paramedics and were subsequently admitted to the central emergency department of the Saarland University Hospital. A standardized data collection form was used to collect information from the emergency service protocol and initial emergency department assessment. The evaluation employed descriptive statistical methods and a total of 207 completed records were analyzed. RESULTS: Both professional groups achieved significant pain reduction and fulfilled the criteria for effective pain management (pain reduction: emergency medical service physicians 5.5 ± 2.0/paramedic 4.4 ± 2.1, p < 0.001). Emergency medical service physicians, however, more frequently attained a higher reduction in numerical rating scale scores and administered oxygen. Notable differences were observed in the range of medications used and the dosages. CONCLUSION: This study could show that prehospital analgesia is comparable between emergency medical service physicians and paramedics in terms of effectiveness for trauma patients if the indications are correctly set, while observing pre-existing instructions. With their competencies paramedics are able to perform an effective and safe analgesic treatment within the framework of preformulated procedural instructions, which can be equal to that of an emergency medical service physician.

Predicting treatment response to ketamine in treatment-resistant depression using auditory mismatch negativity: Study protocol.

BACKGROUND: Ketamine has recently attracted considerable attention for its rapid effects on patients with major depressive disorder, including treatment-resistant depression (TRD). Despite ketamine's promising results in treating depression, a significant number of patients do not respond to the treatment, and predicting who will benefit remains a challenge. Although its antidepressant effects are known to be linked to its action as an antagonist of the N-methyl-D-aspartate (NMDA) receptor, the precise mechanisms that determine why some patients respond and others do not are still unclear. OBJECTIVE: This study aims to understand the computational mechanisms underlying changes in the auditory mismatch negativity (MMN) response following treatment with intravenous ketamine. Moreover, we aim to link the computational mechanisms to their underlying neural causes and use the parameters of the neurocomputational model to make individual treatment predictions. METHODS: This is a prospective study of 30 patients with TRD who are undergoing intravenous ketamine therapy. Prior to 3 out of 4 ketamine infusions, EEG will be recorded while patients complete the auditory MMN task. Depression, suicidality, and anxiety will be assessed throughout the study and a week after the last ketamine infusion. To translate the effects of ketamine on the MMN to computational mechanisms, we will model changes in the auditory MMN using the hierarchical Gaussian filter, a hierarchical Bayesian model. Furthermore, we will employ a conductance-based neural mass model of the electrophysiological data to link these computational mechanisms to their neural causes. CONCLUSION: The findings of this study may improve understanding of the mechanisms underlying response and resistance to ketamine treatment in patients with TRD. The parameters obtained from fitting computational models to EEG recordings may facilitate single-patient treatment predictions, which could provide clinically useful prognostic information. TRIAL REGISTRATION: Clinicaltrials.gov NCT05464264. Registered June 24, 2022.

Exploring the interplay of chronic toxoplasmosis and NMDAR dysfunction: Insights into schizophrenia-like behaviors and therapeutic potential.

Background: Chronic toxoplasmosis has been strongly implicated in the development of psychosis and schizophrenia. Additionally, the understanding of schizophrenia has been significantly reshaped by insights into N-methyl-D-aspartate receptor (NMDAR) hypofunction. Aim: This study aimed to compare the behavioral, antioxidant, and NMDAR changes in mice subjected to Toxoplasma gondii infection and those treated with ketamine to induce schizophrenia-like symptoms. Methods: Sixty male BALB/c mice were divided into six groups: toxoplasmosis (TOXO) (infected), ketamine-induced schizophrenia (KET), TOXO+KET, TOXO+sulfadiazine-trimethoprim treatment (SDT), TOXO+KET+SDT, and control (CON) (uninfected). After 10 weeks post-infection, behavioral tests were conducted, brain antioxidant status and lipid peroxidation were analyzed, and NMDA-NR1/NR2A expressions were assessed. TOXO and KET induced distinct behaviors: hyperlocomotion, anxiety, and memory impairment. Results: Antioxidant enzyme levels decreased, and lipid peroxidation increased in TOXO and schizophrenic mice brains. NMDAR downregulation, especially NR-1 and NR2A, was evident due to T. gondii and ketamine. Sulfadiazine-trimethoprim ameliorated NMDAR downregulation, but not all of the behavioral alterations. Conclusion: Further studies are needed to elucidate specific NMDAR subunit roles in toxoplasmosis-induced pathophysiology, offering potential therapeutic insights. This investigation highlights the intricate relationship between chronic toxoplasmosis, NMDAR dysfunction, and schizophrenia-like behaviors. Insights gained could pave the way for innovative interventions targeting both cognitive and neurological impairments associated with these conditions.